ObjectivesAcute kidney injury (AKI) is a frequent clinical manifestation of severe malaria. Although the pathogenesis of P. falciparum severity is attributed to cytoadherence, the pathogenesis due to P. vivax and P. knowlesi are not very well understood and their presence within the host tissue has not been demonstrated. Therefore, the objective of this study was to determine if P. vivax and P.knowlesi interact with host renal tissue in malarial AKI.
MethodsArchival FFPE renal biopsies from 16 patients having AKI with suspected or confirmed malaria diagnosis, and 5 patients with non-malarial AKI, were subjected to histopathological analysis and DNA extraction. The total DNA from these renal biopsies was used to investigate the presence of the 5 species of human malaria parasite: P. falciparum, P. vivax, P. knowlesi, P.malariae and, P. ovale. The results of histopathology and PCR analysis were analyzed to understand the pathogenesis of malaria associated AKI.
ResultsRenal biopsies from malarial AKI patients were found to harbor DNA from P. vivax (14 of 16), the zoonotic monkey parasite P. knowlesi (7) and P. falciparum (5) in the form of monoinfections as well as mixed infections. Sanger sequencing was used to confirm species identity.Histopathological analysis revealed the presence of microvascular injury as a common feature of P. vivax and P. knowlesi related AKI. Hemozoin could be detected within the renal tissue, which indicated the presence of metabolically active parasites.
ConclusionsP. vivax and P. knowlesi associated AKI may involve interaction of the host renal tissue with parasite derived components such as Plasmodium DNA and hemozoin which may lead to innate immune activation and host tissue injury.